Channelless fluidic sample transport medium

ABSTRACT

A fluidic device ( 100 ) comprising a substrate ( 101 ) and a transport medium ( 103 ) provided on the substrate ( 101 ) to define a transport path for transporting a fluidic sample ( 104 ) driven by an electric force.

This application is the National Stage of International Application No.PCT/EP2006/065047, filed on 3 Aug. 2006 which designated the UnitedStates of America, and which international application was published asPublication No. WO 2008/014825.

BACKGROUND ART

The present invention relates to fluidic devices.

In microstructure technology applications, fluid may be conveyed throughminiaturized channels (which may be filled with gel material) formed ina substrate. For a capillary electrophoresis device as an example forsuch a microstructure technology application, it may be necessary togenerate an electric field in the fluid channels in order to allow for atransport of components of the fluid through the channels using electricforces. Such an electric force or field may be generated by dippingcontact pins of the capillary electrophoresis device into the fluidwhich may be filled in a well defined by a carrier element coupled to amicrofluidic chip, and by applying an electrical voltage to such contactpins.

U.S. Pat. No. 6,509,085 B1 discloses to provide laminates having channelstructures disposed between sheets of the laminate. The channels areraised on a sheet of laminate, typically by printing the structure onthe sheet.

U.S. Pat. No. 5,736,188 discloses a backing sheet provided with apattern of pathways of silica or cellulose by a printing process. Theremay be multiple pathways leading from an eluant application regionmeeting in a merged zone to a detection zone and thence to a wastereservoir. Different pathways may have different fluid traversal timesbecause they differ in length and/or material. Thus analyte and reagentsdeposited at depots on different pathways are sequentially delivered (bycapillary forces, that is to say be a purely internal force) to thedetection zone. Reagents may be applied by printing. The detection zonemay have an electrode assembly, also applied by printing, for detectingthe effects of analyte.

DISCLOSURE

It is an object of the invention to enable a simplified manufactureand/or operation of a fluidic device. The object is solved by theindependent claims. Exemplary embodiments are shown by the dependentclaims.

According to an exemplary embodiment of the invention, a fluidic deviceis provided comprising a substrate (for instance a glass slide) and atransport medium (for instance a gel) provided (for instance printed) onthe substrate to define a transport path for transporting a fluidicsample (for instance a biochemical liquid to be analyzed) driven by anexternal source (for example an electric force by applying an electricvoltage to electric contact pins to be coupled electrically to thetransport medium in an electrophoresis application).

According to another exemplary embodiment, a method of manufacturing afluidic device is provided, the method comprising providing a transportmedium on a substrate of the fluidic device to form a transport path fortransporting a fluidic sample driven by an external (for instanceelectric) force.

The term “external force” may particularly denote any driving mechanismwhich is not intrinsically based on the material of the fluid transportmedium (like pure capillary forces) but which results of an influence ofa force promoting component which is provided externally of or apartfrom the fluid transport medium. For instance, a mechanical (for examplevacuum or pressure) force generator (like a pump) or an electrical forcegenerator (like electrodes connected to a voltage supply) may be used togenerate such an external force.

According to an exemplary embodiment, a transport medium like gel for agel electrophoresis device may be directly deposited onto a for instancecompletely or partially planar surface of a substrate, thereby making itdispensable to provide complex fluidic structures within a surfaceportion of the substrate. In contrast to this, material may simply besputtered, printed, deposited, spotted or adhered onto a surface of asubstrate, thereby forming a fluidic device having elevated structuresas fluid transport structures. The transport medium may be or may be notformed as one or more “elevated structures”.

Electric forces acting on components of a fluidic sample flowing throughthe transport medium may be applied to such a deposited transportmedium, for instance by dipping or pressing electrodes into specificportions of the transport medium path or by forming the transport mediumon top of electrode structures formed in and/or on the substrate,thereby allowing a motion of components of a fluidic sample under theinfluence of such an externally applied electric force. The manufactureof such a fluidic device is very simple and may also allow to providethree-dimensional layer structures for complex or sophisticated fluidtransports.

Therefore, a process and an apparatus for micro- and nanoscalemeasurements, particularly for life science chip technology, may beprovided. In contrast to the conventional need to form channels in asubstrate for micro- and nanotechnology applications which channels thenhave to be filled with gel material or the like before use by a user,exemplary embodiments may require significantly less effort inmanufacture and operation and may be manufacturable with less costs. Incontrast to the manufacture of a complex channel system in whichcorresponding substances may be filled and which substances may beelectrically contacted afterwards, exemplary embodiments may allow tosimply print structures (like gel, dye, buffer, sample, etc.) even on acompletely planar substrate. A fluidic sample may then be conductedunder the influence of an external force through the elevated structureas the transport medium (for example an electric force, additionallymechanical forces generated by a pressure/vacuum, magnetic forcesgenerated by magnets, etc. may be generated as well).

Particularly, using print technologies like the ink-jet technology,varnishing technologies, dispenser technologies (for instance adheringtechnology), pen-like material application technologies (for instance“painting” on a substrate surface with gel material), stamptechnologies, or serigraphy, it may be possible to design a fluidtransport structure by deposition without the need to make use ofchannel walls of the substrate (which may be planar or which may benon-planar, as desired) as a mechanical support. The height of the fluidtransport medium in a vertical dimension can be adjusted by repeatingthe deposition procedure once or several times. Exemplary embodimentsmay have applications in the pico-, nano- and microtechnology.

The deposition and design of the elevated structures in a multilayerprocedure may be performed in a similar manner as with rapid prototypingknown from plastic technology.

According to exemplary embodiments, it is possible to combine fixedstructures with variable structures. Components like electric contactsand a basis may be fixed. The active functional structure of aseparation technology (for instance gel for gel electrophoresisseparation) may be a variable structure which can be adjusted for aspecific application. The entire design of a chip adapted for a specificapplication can be realized in a modular manner as some kind ofconstruction set, in which different modules are available which can becombined in a flexible, user-defined and variable manner.

By such a procedure, it may also be possible to integrate elements ofprocess technology (for instance using valves, pumps and/or othermicrotechnology components). The chip technology (wherein chip mayparticularly denote a chip in the field of application of life science)may thereby be brought to a highly integrative level.

Since very thin layers may be applied (for instance with atomic layerdeposition, ALD), the thickness of the layers may be controlled with anaccuracy of up to one atomic layer), exemplary embodiments may be usedin the field of microtechnology, nanotechnology, and evenpicotechnology.

An electrical connection element or an electrical supply can be formedby depositing electrically conductive structures prior to (or after) theprocess of forming the transport medium. This may even allow depositingactive electric members, for instance a capacitive measurement system,on a substrate. Particularly, when foreseeing such a chip as reusable(for instance by removing the deposited transport medium after usewithout removing deposited electrode structures, for instance for such acapacitive measurement system), the costs for such a system may bereasonable. However, it is also possible that electric supplies or otherelectrical components can be manufactured after manufacturing thetransport medium.

The substrate may comprise one or a plurality of active zones (forinstance portions having specific affinities), sensors, differenttemperature zones, etc., and the microfluidic structure may be simplyprinted on the substrate.

For pressure conduits, vacuum conduits and other supply lines of gas orliquids (that is to say fluids), a part of the transport structures mayalso be manufactured inside of the substrate prior to the ink-jetprocess or other deposition process.

In order to suppress or avoid undesired drying of the transport mediumduring or after manufacture, it is possible to perform the manufactureprocess or operate the device in a saturated steam atmosphere.

After depositing the transport medium (for instance gel) structure, itis possible to cover the substrate with a protection layer (for instancevarnish). By taking this measure, a closed layer may be generated, andalso a closed fluid path guide.

When using an ink-jet technology, it may be possible to design verydifferent zones on the chip, for instance comprising gel and dye, onlygel, gel with additives, or any other fluids and/or solids.

By such a deposition technique, it may also be possible in an easymanner to manufacture fluidic crossings or bifurcations of transportmedium conduits (for instance for mixing fluids, promoting a chemicalreaction between fluids, etc.), as well as three-dimensional structures.

Exemplary embodiments may also be implemented in the context of amultilayer technology. For instance, a layer may first be depositedwhich modifies or adjust the surface properties. After such aconditioning procedure, a patterned layer with the transport medium maybe deposited. It is also possible that multiple structures of thetransport medium are deposited (next to one another on the substratesurface or vertically stacked). It is also possible to design multipletube structures.

Instead of a varnish, it is also possible to provide a cover elementwhich comprises a spacer which may seal the chip and form wells. Intosuch wells, the samples and contacts may then be immersed or dipped.

Such a technology can be used to manufacture multi-purpose ready-to-usechips as well as to manufacture chips which are printed on the clientside (“chip-on-demand”). According to an exemplary embodiment, it ispossible to provide a chip on demand, or in other words to have itprinted right before use at a costumer side. This may also include thepossibility that the customer can design her or his own chip-layouts.

Surface portions of the carrier substrate and/or of the cover elementcan (at least partially) be formed of hydrophobic material so that thesurface portions on which the transport medium shall be deposited may bespatially defined.

The substrate and/or the cover may be configured to be reusable.Recycling used fluidic devices may reduce costs for the analysis.

It is also possible to manufacture transport medium structures having avalve function, wherein such a valve may be operated by a variation ofthe temperature (for instance a part of the printed structures may befreezed or heated).

Pre-printed and (subsequently) freezed structures are shippable easily,and can be conditioned for use by melting.

According to an exemplary embodiment, a fluid transport content, that isto say a transport medium for a fluidic sample, may be applied on acarrier for a chip, particularly for electrophoresis applications. Sucha fluid path content may be a gel which may be deposited in achannelless manner on a surface of a life science chip. Such a fluidicsample may be driven to be moved using an external (electric) energy,particularly using the principle of (gel) electrophoresis. Additionallyor alternatively to an electrophoretic separation, other separationforces like vacuum might be applied (for example evaporation drivenseparation as disclosed as such, for instance, by Manz et al.).

According to an exemplary embodiment, a gradient gel may be applied on asubstrate, for instance using two or more printing nozzles withspatially modifiable mixture ratio of the components emitted by theprinting nozzles.

A substrate having holes or being free of holes may be used, and fluidpath structures may be printed onto the substrate (for instance gelmaterial may be printed thereon). The holes may serve as fluidcontainers but may be partially or entirely filled with fluid transportmedium.

If desired, such a structure may be covered with a protection varnish soas to protect the printed structure for the time between manufacture andactual use. Instead of providing a protection varnish, the substratewith the deposited transport medium may be shock-freezed so as to avoidor delay drying or other deterioration of the transport medium. In thelatter embodiment, a passivation layer, for instance made of varnish,may be omitted. A further alternative is a dried structure of transportmedium deposited on a substrate which dried structure can be humidifieddirectly before use, to condition the chip for a biochemicalapplication.

The substrate may be made of any desired material, like glass, silicon,plastic, ceramics, semiconductor or the like.

The transport medium may be foreseen to be in functional contact withsmall (fluid) containers/recesses formed in the substrate or withconnections for providing an electric contact.

After having deposited a passivation layer over the elevated transportmedium structure, the surface can be planarized or may remainnon-planar.

A substrate with a gel deposited thereon and a passivation layer ofvarnish applied thereon may be a unit which can be conditioned for anactual experiment by removing the passivation selectively from theportions of the substrate covered with the transport medium. For thispurpose, it is possible, for example, to put a caddy or any othercarrier element on top of the chip, wherein the caddy may have one ormore cutting elements or tips for penetrating or destroying specificportions of the varnish, to thereby expose an “active” surface of thechip, namely at least a portion of the surface of the substrate which iscovered with the transport medium.

As an alternative to such a tip, it is possible to foresee the varnishof a material which can be automatically removed when brought in contactwith an aqueous solution. Thus, it is possible to manufacture thevarnish from a water-soluble material. In such a scenario, the entiresurface of the varnish or specific surfaces of the varnish aresacrificed when being contacted with a sample to be analyzed, therebyexposing the transport medium to the fluidic sample, allowing to bringthe fluidic sample in fluid communication with the transport medium.

For example, a transport medium line printed on a substrate may have athickness between 10 μm and 25 μm. A varnish layer may have a dimensionin the order of magnitude of 1 μm. For example, a silicone varnish maybe used as a passivation layer, or a water-soluble varnish.

As a further alternative, it is possible to cover the substrate with thedeposited transport medium structures by a foil. Such a foil may then beremoved by a user before use of the device. The foil may be perforatedor manufactured otherwise in such a manner that when removing the foil,only selective portions of the substrate surface, particularly thesurface portions which are covered with the transport medium, areexposed.

In many cases, alignment markers are manufactured on microfluidic chipsallowing a proper alignment between different substrate layers to beconnected to one another for forming such fluidic chips. Such alignmentmarkers may also be printed on or deposited otherwise on a surface ofthe substrate, for instance during the same procedure during which thetransport medium structures are provided. This may allow to simplifymanufacture. When the alignment markers shall be optically visible, itis also possible to mix the material for the transport medium with a dyefor application of the mixture on the substrate as the alignmentmarkers.

According to an exemplary embodiment, a hydrophobic/hydrophilic patternmay be applied or deposited on the substrate, thereby enabling a fluidicsample to be present only in specific portions of the surface of such asubstrate. Also the Lotus effect may be taken into account for definingsurface portions which shall be deposited with the fluidic sample, andsurface portions which shall remain free of the fluidic sample. Byproviding microstructures with special dimensions on the surface, thefluid repellant property as known from the Lotus plant may be used.

Wells may be formed in a caddy structure which can be provided centrallyor laterally on a chip. Therefore, via such wells, a fluidic sample maybe filled in the microfluidic chip device. Metallic contacts (like pins)for electrically contacting the transport structures so as to generatean electric or electromagnetic force driving the fluidic sample throughthe transport medium may be provided on a main surface of the substrate,or may be also foreseen at lateral contact areas of the substrate.Particularly when a cover element is put on top of a substrate on whichthe transport medium has been deposited, the resulting device may alsobe suitable for pressure-driven or vacuum-driven applications (or anyother external force), like pressure-driven liquid chromatographyseparation applications. For this purpose, a pressure may be applied toend portions of the transport medium, thereby forcing a fluidic sampleto move through the transport medium.

According to exemplary embodiments, it may also be possible tomanufacture “negative” structures. For such a purpose, sacrificialtransport medium layers may be applied to the substrate and may bepassivated by a varnish. Afterwards, the sacrificial material may beremoved, for instance by evaporating them through the cover layer as aconsequence of an appropriate thermal treating.

It may be advantageous that the substrate and/or the transport medium isoptically transparent, particularly for optical detection methods likefluorescence detection. For example, the carrier may be a substrate madeof glass, quartz, or PMMA or any other polymer (which may have a smalloptical background).

Therefore, according to an exemplary embodiment, a ready-to-use chip maybe provided on which a user does not have to insert manually gelmaterial in a complex channel structure but use a readily manufacturedfluid transport structure which is already pre-printed on a surface ofthe substrate. It may be dispensible that the user has to condition thetransport medium for use (for instance by humidifying it, or byselectively removing portions of a passivation layer covering thetransport medium).

Exemplary embodiments may use containers or samples in the dimension ofpicoliters, nanoliters, microliters, or milliliters.

The transport medium may be formed by any deposition procedure or by anyprinting procedure. For instance, ink-jet, bubble jet, serigraphy,nozzle deposition, rollerball deposition with a two-dimensional scanningon a surface substrate, or the generation of hydrophilic/hydrophobicpatterns may be implemented. After having manufacturedhydrophilic/hydrophobic patterns by printing or any other procedure, itmay be dipped into an emersion bath. For instance, a fluid of theemersion bath may only remain on hydrophilic portions of such a pattern.

It is also possible to provide transport medium based valves forswitching between different fluid path configurations. For this purpose,a swellable substance may be provided on the substrate, bridging twotransport medium conduits when the swellable substance is in a swollenoperation mode, and disconnecting the structures when the swellablesubstance is in a non-swollen operation mode. As an alternative to amoisture-based expansion, a temperature-based expansion or compressionmay be realized.

According to an exemplary embodiment, a lab-on-chip may be formed inwhich different procedural components like mixing of samples, reaction,separation, etc. may be combined on a single fluidic chip.

Next, further exemplary embodiments of the fluidic device will beexplained. However, these embodiments also apply to the method formanufacturing a fluidic device.

It is possible that the transport medium comprises a non-trenched wall.The term “non-trenched wall” may particularly denote a wall which is notdefined entirely by a trench formed in a substrate, but which is definedby the transport medium itself. At least a part of the lateral wall ofthe transport medium may be free of an external mechanical support, andmay be supported by the intrinsic material properties of the transportmedium (for instance being in a gel-like phase). Therefore, thetransport medium may comprise a channelless wall, that is to say a wallwhich does not necessarily need a side wall of a channel formed in thesubstrate for mechanical support.

However, it is possible that at least a part of the transport medium isdeposited in a channel structure. At least of the lateral portionbetween the transport medium and the surrounding channel structure maybe free from a direct contact or mechanical support between thetransport medium and the surrounding channel structure.

The transport medium may be free of a lateral mechanical support by thesubstrate along at least a part of a lateral wall of the transportmedium. Such an at least partially channelless wall may be defined by anedge portion of the transport medium itself. For instance, a materialproperty, for instance viscosity, of the transport medium itself may beselected and adjusted in such a manner that, when being deposited on thesubstrate, the edge portion remains mechanically stable and does notdistribute the material of the transport medium over the entire surfaceof the substrate. Therefore, a self-supporting structure may be formedas the transport medium.

The channelless wall may be formed independently of a sub-surface trenchin the substrate. Therefore, even if a trench is formed in thesubstrate, lateral side walls of this trench do not define or limit thelateral extension of the transport medium.

At least one recess may be formed in the substrate and may be in fluidcommunication with the elevated transport medium conduits. Such recessesmay be fluid containers or buffer containers or waste containers whichmay supply the transport medium with fluidic sample or other components.

According to an embodiment, the transport medium may be in a dried stateand may be foreseen to be humidified before being capable oftransporting the fluidic sample. By drying the transport medium, thestorage of the fluidic device for a long time between manufacture andactual use may be made possible. Consequently, the fluidic device may bedelivered to a client “ready to use”, and the client may activate thefluidic device for an actual experiment with low effort, simply bycontacting a surface of the fluidic device with water, an aqueoussolution or into a water vapor saturated environment to humidify thedried transport medium.

Additionally or alternatively, a passivation layer may cover at least apart of the transport medium. Such a passivation layer may mechanicallyprotect the transport medium against an environment, and may avoiddrying of the transport medium. The passivation layer may comprise atleast one material of the group consisting of a varnish, silicone and awater-soluble material. Such a passivation layer may be selectivelyremoved or destroyed for exposing an active surface of the fluidicdevice.

The fluidic device may comprise a carrier element having a well. Thecarrier element may be adapted to be connected to the substrate in amanner to enable external access to the transport medium through thewell. The well may then allow a needle or a pipette or any other fluidemitting tip to insert a fluidic sample to be brought in contact withthe transport medium. Such a well may have the shape of a hollowcylindrical structure in a plate defining a path along which the fluidto be supplied to the transport medium is brought in contact with thesurface of the fluidic device. However, the use of such a carrierelement or caddy is merely optional, and a carrier element may beomitted according to exemplary embodiments. For instance, a removablefoil may be provided on a chip. When removing the foil, selectiveportions of the chip may be exposed. Such exposed portions may then beprovided with a drop of sample, buffer, or the like.

The carrier element may comprise one or more tips (for instance acutting element) located and designed to penetrate through thepassivation layer in an operation state in which the carrier element isconnected to the substrate. Therefore, when a user clicks a carrierelement onto the fluidic device to make the fluidic device ready for anexperiment, the tip may automatically penetrate the passivation layer soas to expose the transport medium.

Alternatively, the passivation layer may be configured to beautomatically removable when the passivation layer is brought in contactwith a fluid, for instance when a fluidic sample is filled in the well.

Further alternatively, a removable foil may be provided covering thesubstrate and the transport medium. The foil may be adapted toselectively expose at least one surface portion of the transport mediumwhen removing the foil. Therefore, a plastic foil which can be removedand which has perforated and adhering surface portions may defineportions of the surface which can be exposed by removing the foil, andother surface portions which remain covered by the foil, so that thefoil can still fulfill its protecting function at the remainingportions. Even more simple, a detachable and even reusable cover elementmay be provided.

At least one alignment marker may be provided on the substrate and maycomprise the same material as the transport medium. This may enable tomanufacture alignment markers and the fluid conduits in one commonmanufacturing procedure. Since the alignment marker may be used foroptically aligning the substrate with respect to another substrate (forinstance when manufacturing a multi-substrate comprising fluidicdevice), it may be advantageous that the alignment material additionallycomprises a dye material. For example, the alignment marker may then bea gel to which dye material is added.

The transport medium may comprise at least two portions separated fromeach other by a swellable material which, in a first operation state,enables a fluid communication between the at least two portions via theswellable material, and, in a second operation state, disables a fluidcommunication between the at least two portions via the swellablematerial. Such a swellable material which may be swollen by a thermic ora fluidic trigger scheme. It may serve as a fluidic valve forselectively connecting or disconnecting different conduits formed by thetransport medium. Therefore, a switch between different fluid pathconfigurations is possible.

The transport medium may adhere to the substrate, so that the fluidicdevice is very stable and robust. Thus, the transport medium and thesubstrate may be configured so that a bonding or stable connectionbetween the transport medium and the substrate is enabled. For instance,forming micro-elevations of electrophoresis gel material on a glasssubstrate is a good combination.

The transport medium may be adapted for transporting the fluidic sampledriven by an externally applicable electric force. Such an electricalforce may be applied by a voltage supply unit supplying contacts to bebrought in physical and electrical contact with the transport mediumwith electric energy. In other words, electric fields may be generatedwithin the deposited transport medium.

The fluidic device may comprise one or more electric contacts to beconnected to the transport medium. Such a contact may be formed directlyon or embedded in the substrate before depositing the transport medium.This may allow to simply wash off the transport medium after use torecycle the fluidic device. Then, the electric contacts may be usedagain, and new transport medium material may be deposited on thecontacts again.

Alternatively, such electric contacts may be provided as separatecomponents (like pins) and may be dipped into the transport medium ormay be provided or dipped in recesses formed as fluid containers.

The transport medium may comprise a gel material, particularly agradient gel material. A gradient gel may be used for electrophoresisapplications and may gradually modify the chemical properties of the gelalong an extension of a fluidic conduit, thereby allowing to selectivelyseparate or immobilize different fractions of a fluidic sample within agel strip.

The fluidic device may be adapted as a fluidic chip device. In otherwords, the components of the (life science) fluidic chip may be providedon and/or in the chip-like substrate, for instance a glass substrate.This may allow for a miniature manufacture of the fluidic device.

Particularly, the fluidic device may be adapted as a fluid separationdevice. Therefore, different components of a fluid may be separated whenbeing transported under the influence of an external electric field orforce along the transport medium structures.

Particularly, the fluidic device may be adapted as an electrophoresisdevice. The field of electrophoresis may denote the separation ofdifferent components of a fluidic sample due to different affinitiesbetween components of the sample and a chemical environment and due todifferent electrical charge properties of components of the sample in asurrounding chemical environment, like a gel.

The fluidic device may be adapted as a microfluidic device. The term“microfluidic device” may particularly denote a fluidic device asdescribed herein which allows to convey fluid through micropores, thatis pores having a dimension in the order of magnitude of micrometers orless.

The fluidic device may further be adapted as a nanofluidic device. Theterm “nanofluidic device” may particularly denote a fluid device asdescribed herein which allows to convey fluid through nanopores, that ispores having a dimension in the order of magnitude of nanometers orless.

The fluidic device may also be adapted as a picofluidic device. The term“picofluidic device” may particularly denote a fluidic device asdescribed herein which allows to convey fluid through picopores, that ispores having a dimension in the order of magnitude of picometers.

The fluidic device may be adapted to transport a fluidic samplecomprising at least one of the group consisting of antibodies, achemical and/or biological relevant substance, and a dye. Thus, thefluid may also comprises, for instance, a mixture (or pure part) withladder, antibodies, chemical relevant substances, dyes, etc.

The fluidic device may further comprise at least one channel formed inthe substrate for channeling the fluidic sample. Therefore, even if thetransport medium is applied by deposition or printing techniques to asurface of the substrate, it is nevertheless possible that at least apart of the transport medium is provided within channels, however stillhaving the capability due to its intrinsic material properties to besupported in a self-employed manner. In other words, lateral walls ofsuch a channel may be not essential or do not contribute to the lateraldefinition and stability of the transport medium.

The fluidic device may comprise at least one fluid path formed in thesubstrate and filled with the transport medium for channeling thefluidic sample, wherein the at least one fluid path may be in fluidcommunication with the transport medium provided on the substrate. Bysuch a configuration, fluid communication between transport mediumportions out of fluid paths and transport medium portions within a fluidpath may be made possible.

The substrate may comprise an optically transparent material to enableoptical detection of separated components, for instance to detectdifferent spatially separated bands of fractions of a sample in anelectrophoresis strip. Such a substrate may comprise a glass, a quartz,or a plastics material like PMMA.

The fluidic device may be adapted to analyze at least one of the groupconsisting of a physical, a chemical and a biological parameter of atleast one component of the fluidic sample. The term “physical parameter”may particularly denote a size or a temperature of the fluidic sample.The term “chemical parameter” may particularly denote a concentration ora fraction of the analyt, an affinity parameter, or the like. The term“biological parameter” may particularly denote a concentration of aprotein, a gene or the like in a biochemical solution, a biologicalactivity of a component, etc.

The fluidic device may comprise at least one of a sensor device, adevice for chemical, biological and/or pharmaceutical analysis, acapillary electrophoresis device, an electronic measurement device, anda mass spectroscopy device. More generally, the fluidic device may beapplied in any technical application in which an electrically and/ormagnetically driven fluid transport mechanism using an external force isimplemented.

In the following, further exemplary embodiments of the method formanufacturing the fluidic device will be explained. However, theseembodiments also apply to the fluidic device.

The method may comprise depositing the transport medium on thesubstrate. Such a deposition procedure may denote any procedure on whichthe transport medium is not only injected in fluid paths formed in asubstrate, but in which the transport medium is applied onto at leastone surface of a substrate. Particularly, such a deposition techniquemay include a printing technique, like serigraph, ink-jet, bubble-jet,intaligo, offset printing, thermal laser printing, stamping, varnishing,and dispensing. Printing is very easy, cheap and is properlycontrollable in a spatial manner so as to make it possible tomanufacture the fluidic device with low cost.

The method may comprise providing the transport medium with a materialgradient along the substrate, for example by mixing a plurality ofcomponents in a spatially dependent manner along an extension of thesubstrate. For instance, two nozzles or two print heads may provide twoor more different components in a spatially dependent manner, therebymaking it possible to manufacture a gel gradient transport medium or thelike with low effort.

The method may comprise freeze-drying, quick-freezing, or shock-freezingthe transport medium before, during or after deposition on thesubstrate. By performing such procedures, it may be possible to generatea fluidic device which can be stored a long time before being actuallyused for a fluid analysis experiment. For use, the fluidic device maythen be melted, and may additionally be humidified to condition it forsubsequent use.

The method may comprise applying a pattern of hydrophilic andhydrophobic portions on the substrate, thereby defining pathways for thefluidic sample when being applied to the fluidic device. When thefluidic sample is based on water (for instance is an aqueous solution),it will be accumulated in hydrophilic portions, and essentially no waterwill remain in hydrophobic portions. Therefore, by covering differentsurface portions with different materials may allow to define fluidpathways.

The method may comprise covering at least a part of the transport mediumwith a passivation layer. This may be performed to protect the transportmedium from an undesired external influence.

At least a part of the transport medium covered with the passivationlayer may be selectively removed, particularly for making the fluidicdevice ready for use.

The method may further comprise providing the transport medium on thesubstrate in a saturated vapor environment. This may allow tomanufacture the transport medium with high quality, since drying (whichmay be preferred in exemplary embodiments) may be suppressed orprevented.

It is also possible that a ‘channelless wall’ can also be implemented ina 3D structure (like a spider web). For instance, it is possible to usethe ultra thin fibers of a spider web as separation paths.

According to an exemplary embodiment, three-dimensional structures canbe realized (for example bond-contacts from the gel to electricalcontact pads).

According to another exemplary embodiment, a foil may be provided with,for instance, pads with electrical extensions on it. This is foil may bethen, on demand, printed with at least one separation channel. With acapillary or any other device will then the sample be injected directlyin the fluid (for example 40 pl like the sample plug in existing chips).And then, the sample may be separated with capillary electrophoresis.

Embodiments of the invention are not limited with regard to any specificoperation mode, but any driving scheme implementing external forces maybe used. The layout of the fluidic structure is variable (2D or 3D). Itis possible to provide individual fluid transport structures or complexnetworks thereof. The fluid transport medium may be entirely active, ormay be a mixture of active an passive (inactive) components.

BRIEF DESCRIPTION OF DRAWINGS

Objects and many of the attendant advantages of embodiments of thepresent invention will be readily appreciated and become betterunderstood by reference to the following more detailed description ofembodiments in connection with the accompanied drawings. Features thatare substantially or functionally equal or similar will be referred toby the same reference signs.

FIG. 1 to FIG. 4 show fluidic devices according to exemplary embodimentsof the invention.

The illustration in the drawing is schematically.

In the following, referring to FIG. 1, a fluidic device 100 according toan exemplary embodiment of the invention will be explained.

FIG. 1 shows a cross-sectional view of the fluidic device 100 which is agel electrophoresis device.

The fluidic device 100 comprises a glass substrate 101 in which a recess102 has been formed, for instance by etching. A gradient gel strip 103is deposited as a fluid transport medium on the glass substrate 101 todefine a transport path for transporting a fluidic sample 104 driven byan electric force.

Although a central portion of the transport medium 103 is alsopositioned in the recess 102, the major portion of the transport medium103 is deposited on a planar surface of the substrate 101 by printing.Therefore, the transport medium 103 is free of a lateral support by thesubstrate 101 along the major part of a lateral wall of the transportmedium 103 (which cannot be seen in FIG. 1).

A passivation layer 105 made of a varnish and having a thickness of forexample 1 μm is deposited over an entire surface of the substrate 101which is partially covered with the transport medium 103. Thepassivation layer 105 therefore covers the substrate 101 and thetransport medium 103.

A carrier element 106 is provided as a mechanical support element andcomprises a tubular section 107 defining a well 108. The carrier element106 can be clicked onto the substrate 101 covered by the transportmedium 103 and the passivation layer 105 in a manner to enable externalaccess to the transport medium 103 via the well 108, as will beexplained in more detail in the following.

As can further be taken from FIG. 1, a metallic tip or cutting element109 is foreseen in a lower portion of the carrier element 106 connectedto a lower portion of the tubular element 107. It is adapted topenetrate through the passivation layer 105 in the operation state shownin FIG. 1 in which the carrier element 106 is connected to the substrate101. Thereby, the tip 109 selectively destroys a portion of thepassivation layer in an environment of the well 108.

In the tubular section 107, the fluidic sample 104 to be analyzed orexamined can be filled in the device 100 using a pipette, a fluid supplyneedle of an autosampler or of a fractioner, or the like.

The passivation layer 105 may also be made of a water-soluble varnish sothat the fluidic sample 104 in contact with the varnish 105 selectivelyremoves the varnish 105 in an area of the tubular well 107.

Furthermore, an electric contact 110 connected to an electric voltagesupply unit 111 is dipped in the fluidic sample 104 so as to generate anelectric field in the fluid carrying components fluidic device 100. Thiselectric field is needed for performing a gel electrophoresisseparation.

The gradient gel 103 adheres to the substrate 101. The gradient gel 103is further adapted for transporting the fluidic sample 104 driven by anexternally applicable electric force generated by the electric contactpin 110 to which an electric voltage is applied by the electric voltagesupply unit 111.

The glass substrate 101 is optically transparent so as to enable anoptical read out (for instance performing a fluorescence measurements orthe like) of different fractions of the fluidic sample which may beseparated along an extension of the gradient gel structure 103.

When a sample 104 is filled in the well 108 and is brought incontact—due to the spatially restricted removal of the passivation layer105 when being contacted with the sample 104—with the elevated gradientgel strip 103, an applied electric force (generated by applying avoltage to the tip 110) will force charged components in the fluidicsample 104 to move along an extension of the gel strip 103, therebyseparating different components of the fluidic sample 104. Afterseparation, the different fractions of the fluidic sample 104 may bedetected optically (not shown in FIG. 1), for instance by a fluorescencedetection arrangement.

In the following, referring to FIG. 2, a cross-sectional view of afluidic device 200 according to another exemplary embodiment will beexplained.

The fluidic device 200 is formed on a glass substrate 101.

A first transport medium conduit 201, a second transport medium conduit202 and a third transport medium conduit 203 which are formed aselongated conduits deposited on top of a surface of the substrate 101are shown. In a direction perpendicular to the paper plane of FIG. 2,the structures 201 to 203 extend along a dimension which is essentiallylarger than a cross-sectional dimension in the paper plane of FIG. 2.

The structures 201 to 203 are formed by a printing procedure by moving aprint head in a controlled manner along a two-dimensional scanningsurface of the substrate 101, selectively depositing gel material forforming the conduits 201 to 203.

The first and the third conduits 201 and 203 are directly applied onto aplanar portion of the substrate 101 as non-trenched walls or channellesswalls which are free of any lateral mechanical support by the substrate101. In other words, the channelless wall 204 of the conduits 201 to 203provide a sufficient degree of mechanical stability of the structures201 to 203, particularly of the lateral stability of these structures201 to 203. As can further be taken from FIG. 2, the first and the thirdconduits 201, 203 are formed on planar portions of the surface 201,whereas the conduit 202 is printed partially in a recess 102 formed inthe substrate 101. However, also this second conduit 202 essentiallyprovides the lateral mechanical support by itself, without a need oflateral walls of the recess 102.

Still referring to FIG. 2, the transport medium structures 201 to 203are formed by ink-jet printing, whereas the passivation layer 105 isformed as a continuous layer over the surface of the substrate 101 onwhich the structures 201 to 203 have been deposited. The deposition ofthe passivation layer 105 may be performed by any planar depositionprocedure, like Chemical Vapor Deposition (CVD), Plasma EnhancedChemical Vapor Deposition (PECVD), or Atomic Layer Deposition (ALD).

FIG. 3 shows a plan view of a fluidic device 300 according to anexemplary embodiment.

Structures 201 to 203 are shown as well in this plan view, whereas apassivation layer 105 is omitted in the embodiment of FIG. 3.

After having deposited the structures 201 to 203, they are shock-freezedby cooling so as to be brought in a state in which drying of the gelmaterial of the transport medium structures 201 to 203 is avoided ordelayed.

Furthermore, first alignment markers 302 shaped as strips and a secondalignment marker 303 shaped as a circle are applied to the surface ofthe substrate 201. The alignment markers 302, 303 serve for positioningthe substrate 101 with regard to another substrate (not shown) whenthese two substrates shall be bonded together, for instance. For thispurpose, the alignment markers 302, 303 should be visually inspectable.To provide this function, the structures 302, 303 are printed on thesurface of the substrate 101 during the same procedure by which thestructures 201 to 203 are printed on the substrate 101. However, thematerial used for depositing the alignment markers 302, 303 is fluidseparation gel which comprises additionally a dye material.

Furthermore, FIG. 3 shows enlarged cross-sectional views of portions ofthe fluidic device 300.

As can be taken from the enlarged cross-sectional view of the thirdconduit structure 203, the lateral walls 204 of this conduit 203 aremechanically stable intrinsically without external support, and a lowerportion of the gel material is fixedly connected and adheres in amechanically fixed manner on a surface of the substrate 101.

As can further be taken from the enlarged cross-sectional view of thealignment markers 302, the lateral walls of these alignment markers 302are mechanically stable intrinsically without external support, and alower portion of the gel material is fixedly connected and adheres in amechanically fixed manner on a surface of the substrate 101.

For using the fluidic device 300 for an electrophoresis experiment, itis possible to melt the shock-freezed apparatus 300, and optional tohumidify it in order to condition it for an experiment.

In the following, referring to FIG. 4, a fluidic device 400 according toan exemplary embodiment will be explained.

FIG. 4 shows the fluidic device 400 in a partially disassembled state.

It comprises a chip component 401 and a carrier element 402.

The chip component 401 comprises a glass substrate 101 on which two gelstructures 103 (one of which is bifurcated) are formed by e.g. printing.On the top of this structure, a passivation layer 105 of a varnishmaterial is deposited.

The carrier element 402 comprises a plurality of wells 108. Each of thewells 108 has an assigned sharp tip or cutting element 109. In a similarmanner as shown in FIG. 1, and as indicated by arrows 403, the carrierelement 402 can be attached to the chip element 401 by clicking or usinga snap-fit connection, which can be promoted by a fastening element 404which can be brought in alignment with a lower surface of the substrate101. When a user clicks the carrier element on the chip component 401,the sharp tips 109 automatically penetrate the varnish layer 105. When afluidic sample is filled in the wells 108, the fluidic sample can bebrought in fluid communication with the partially exposed transportmedium structures 103.

It should be noted that the term “comprising” does not exclude otherelements or features and the “a” or “an” does not exclude a plurality.Also elements described in association with different embodiments may becombined. It should also be noted that reference signs in the claimsshall not be construed as limiting the scope of the claims.

1. A fluidic device comprising: a substrate; a transport medium providedon the substrate and at least partially covered by a passivation layer,wherein the transport medium defines a transport path for transporting afluidic sample driven by an external force; and a carrier element havinga well, wherein the carrier element is adapted to be connected to thesubstrate in a manner to enable external access to the transport mediumthrough the well, wherein the carrier element comprises a tip locatedand designed to penetrate through the passivation layer when the carrierelement is connected to the substrate.
 2. The fluidic device of claim 1wherein the transport medium comprises a non-trenched wall; or thetransport medium is free of a mechanical support; or the transportmedium is free of a lateral mechanical support by the substrate along atleast a part of a lateral wall of the transport medium.
 3. The fluidicdevice of claim 1, wherein the transport medium comprises a channellesswall.
 4. The fluidic device of claim 3, wherein the channelless wall isdefined by an edge portion of the transport medium; or the channellesswall is formed functionally independently of a sub-surface trench in thesubstrate.
 5. The fluidic device of claim 1, comprising at least onerecess formed in the substrate and being in fluid communication with thetransport medium.
 6. The fluidic device of claim 1, wherein thepassivation layer comprises at least one material of the groupconsisting of a varnish, silicone, and a water-soluble material.
 7. Thefluidic device of claim 1, further comprising a detachable cover,covering at least a part of the substrate and at least a part of thetransport medium.
 8. The fluidic device of claim 1, further comprisingat least one alignment marker provided on the substrate and comprisingthe same material as the transport medium, wherein the at least onealignment marker additionally comprises a dye material.
 9. The fluidicdevice of claim 1, wherein the transport medium comprising at least twoportions separated from each other by a swellable material which, in aswollen state, enables a fluid communication between the at least twoportions via the swollen material, and, in a non-swollen operationstate, disables a fluid communication between the at least two portionsvia the swellable material; or the transport medium adheres to thesubstrate; or the transport medium is adapted for transporting thefluidic sample driven by an electric force; or wherein the transportmedium is adapted for transporting the fluidic sample driven by anexternally applicable electric force.
 10. The fluidic device of claim 1wherein the fluidic device comprises an electric contact to beelectrically coupled to the transport medium; or the fluidic devicecomprises an electric contact to be electrically coupled to thetransport medium via the fluidic sample; or the transport mediumcomprises a gel; or the transport medium comprises a gradient gel or gellike fluid; or the fluidic device is adapted as a fluidic chip device;or the fluidic device is adapted as a fluid separation device; or thefluidic device is adapted as an electrophoresis device; or the fluidicdevice is adapted as a gel electrophoresis device; or the fluidic deviceis adapted as a microfluidic device; or the fluidic device is adapted asa nanofluidic device; or the fluidic device is adapted as a picofluidicdevice; or the fluidic device is adapted to transport the fluidic samplecomprising at least one of the group consisting of antibodies, achemical relevant substance, a biological relevant substance, and a dye;or the fluidic device comprises at least one channel formed in thesubstrate for channeling the fluidic sample; or the fluidic devicecomprises at least one channel formed in the substrate and filled withthe transport medium for channeling the fluidic sample, wherein the atleast one channel is in fluid communication with the transport mediumprovided on the substrate; or the substrate comprises an opticaltransparent material; or the substrate comprises at least one materialof the group consisting of glass, a semiconductor material, a plasticsmaterial, PMMA, a ceramics material and a metallic material; or thefluidic device is adapted to analyze at least one of the groupconsisting of a physical, a chemical and a biological parameter of atleast one compound of the fluidic sample; or the fluidic devicecomprises at least one of a sensor device, a device for chemical,biological and/or pharmaceutical analysis, a capillary electrophoresisdevice, an electronic measurement device, and a mass spectroscopydevice.
 11. The fluidic device of claim 1, wherein the passivation layeris selectively removed or destroyed to expose an active surface of thesubstrate.